It is known that dsRNA is an agonist of Toll-like receptor 3 (TLR-3), and that RNA, in particular dsRNA, triggers RIG-l-like receptors (RLRs, e.g. MDA-5), in particular RIG-I (retinoic inducible gene I), if a free triphosphate group is present on the RNA. Certain dsRNAs having TLR-3 and RIG-I agonizing activities are disclosed in co-pending International Patent Applications No. PCT/EP2012/071640 and No. PCT/EP2012/071641.
Macrophages and dendritic cells (DCs) take up, e.g. immunomodulatory molecules such as dsRNA by macropinocytosis. However, cells not implicated in mounting an immune response cannot take up dsRNA molecules, and are therefore not amenable for TLR-3 (located in endosomes) or RLRs, more specifically RIG-I (located in the cytoplasm) activation.